Ultrasound provides safe treatment

Researchers from Tech and Emory University have discovered that ultrasound can deliver drugs into human cells. This discovery is a significant development in the field of gene therapy and disease treatment. Both the National Institutes of Health (NIH) and the National Science Foundation (NSF) granted awards to Georgia Tech to carry out the research.

Mark Prausnitz of the School of Chemical and Biomolecular Engineering was one of the primary researchers on this project.

"The goal of this research is to drive drugs, genes and other molecules selectively into cells in the body in a non-invasive way," Prausnitz said.

He and his colleagues found that just as ultrasound can be focused non-invasively within the body to image a fetus, it could be used to propel drugs into tissues without harming the body.

Most of the ultrasound research was conducted with prostate cancer cells. The main question surrounding this phenomenon is why the ultrasound is able to deliver these molecules into the cells to obtain better therapy and gene expression in the process.

"We think the answer is that ultrasound is able to make holes in cell membranes, holes that are subsequently able to reseal themselves by an active process that the cell undergoes," Prausnitz said.

Holes are made in the cells because ultrasound is an oscillating pressure wave that causes gas bubbles to oscillate in a process called cavitation. These gas bubbles ultimately collapse and emit a shock wave and other energy that impact the cell membrane. The impact allows a piece of the cell membrane to be physically ripped off.

At this point, according to Prausnitz, things can go in through the hole, which is generally the goal, and things can come out through the hole, which is not necessarily good. However, the cell actively responds to the presence of a hole by resealing it with intracellular lipid vesicles that are brought to the site of the hole within a few minutes.

This new ultrasound technology has a number of health benefits, one being its role in gene therapy. Prausnitz is cautious in confirming the current level of progress in this field, arguing that current developments in gene therapy are not up to par.

"We are not there yet, and one of the main reasons we're not there yet is delivery," Prausnitz said.

Viruses have been used as a means of delivering genes into cells, but the process entails a clear safety hazard for the receiver of the virus. Ultrasound may be a safer and less invasive alternative to viral gene delivery.

"It does not involve the dangers of viruses but can help drive DNA into cells and get that DNA to be expressed by that cell," Prausnitz said.

Ultrasound is also useful in treating cancer, particularly when chemotherapy is needed to treat a tumor. Chemotherapeutics, however, have well-known side effects. According to Prausnitz, if you can make the tissue more permeable locally inside the tumor by making these holes in the cells, the drug can penetrate that localized spot with very efficient killing of the tumor without getting into other tissues in the body.

Before working at Tech, Prausnitz researched a similar process called electroporation. Electroporation is the application of a brief electric pulse that destabilizes cell membranes and allows for the molecules to enter in the cell. This method is helpful in gene therapy and chemotherapy, but it has limitations.

"One of the big limitations is that unless you want to treat the surface of the body, the skin, then you need to be invasive and introduce electrodes deeper into the body," Prausnitz said.

This illustrates the benefit of ultrasound therapy, which has similar effects to that of electroporation but without invading the body.

The challenge of research is maintaining motivation to keep working.

"What really motivates us at the end of the day is the hope that ultrasound can be used as a real therapy to deliver real drugs and treat real diseases," Prausnitz said.